Treatment of pituitary Cushing disease with a selective CDK inhibitor, R-roscovit

描述（由申请人提供）：我们从创新的实验室研究中发现了r -罗斯科维汀，这是一种选择性CDK抑制剂，具有抑制垂体促皮质瘤细胞增殖和ACTH产生的双重作用。我们现在提出一项试点，概念验证II期临床试验，用r -罗斯维汀治疗从雪松-西奈医学中心垂体中心招募的皮质促性肿瘤（库欣病）患者，以确定r -罗斯维汀是否可以通过减少垂体皮质促性肿瘤ACTH的产生而安全地使尿中游离皮质醇水平正常化。r -罗斯科维汀已经对几种恶性肿瘤进行了I期和II期临床试验，如果对皮质激素肿瘤有效，其口服给药途径和相对轻微的副作用使库欣病的日常长期治疗成为可能。我们的研究将探索一种新的药物治疗策略，直接针对垂体促皮质瘤，最具挑战性的人类神经内分泌疾病之一。

DESCRIPTION (provided by applicant): Our discovery from innovative laboratory research has led to the identification of R-roscovitine, a selective CDK inhibitor with dual effect suppressing both cell proliferation and ACTH production in pituitary corticotroph tumors. We now propose a pilot, proof of concept phase II clinical trial to treat with R-roscovitine of patiens with corticotroph tumors (Cushing disease), who are recruited from the Pituitary Center at Cedars-Sinai Medical Center, to determine if R-roscovitine can safely normalize urinary free cortisol levels by reducing pituitary corticotroph tumor ACTH production. R-roscovitine has been undergoing phase I and II clinical trials for several malignancies, and, if effective for corticotrph tumors, its oral dosing route and relatively mild side effects make daily long-term treatment of Cushing disease feasible. Our study will explore a novel intervention for much needed pharmaco-therapeutic strategies directly targeting pituitary corticotroph tumors, one of the most challenging human neuroendocrine diseases.